3,672 research outputs found

    Traditional tales and imaginary contexts in primary design and technology: a case study

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    Working with contexts is a key component to design and technology activity and education. The most recent iteration of the national curriculum programme of study for design and technology, in England, sets out that children between the ages of 5 and 7 “should work in a range of relevant contexts” (DfE, 2013: 193); suggested contexts including “home and school, gardens and playgrounds, the local community, industry and the wider environment”. Whilst these are real world and familiar contexts, fictional contexts also provide opportunities for developing “creative spaces” in which to speculate and discuss. This intrinsic case study explores the work of two primary teachers’ development of a design and technology activity, where traditional tales provide the context. Children explore design problems and opportunities through the eyes of the Billy Goats Gruff, as they seek assistance to cross the river. Data was gathered through semi-structured interviews and document analysis of children’s design work. The case study reveals how multidisciplinary and imaginative approaches to teaching and learning in the primary classroom simulate and nurture design thinking, dialogue and critique

    Proteomics: in pursuit of effective traumatic brain injury therapeutics

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    Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

    DHODH modulates transcriptional elongation in the neural crest and melanoma

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    Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

    Classificação do atendimento pré-hospitalar pediátrico como instrumento para otimizar a alocação de recursos no atendimento do trauma na cidade de São Paulo, Brasil

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    PURPOSE: To evaluate the pediatric prehospital care in São Paulo, the databases from basic life support units (BLSU) and ALSU, and to propose a simple and effective method for evaluating trauma severity in children at the prehospital phase. METHODS: A single firemen headquarter coordinates all prehospital trauma care in São Paulo city. Two databases were analyzed for children from 0 to 18 years old between 1998 and 2001: one from the Basic Life Support Units (BLSU - firemen) and one from the Advanced Life Support Units (ALSU - doctor and firemen). During this period, advanced life support units provided medical reports from 604 victims, while firemen provided 12.761 reports (BLSU+ALSU). Pre-Hospital Pediatric Trauma Classification is based on physiological status, trauma mechanism and anatomic injuries suggesting high energy transfer. In order to evaluate the proposed classification, it was compared to the Glasgow Coma Score and to the Revised Trauma Score. RESULTS: There was a male predominance in both databases and the most common trauma mechanism was transport related, followed by falls. Mortality was 1.6% in basic life support units and 9.6% in ALSU. There was association among the proposed score, the Glasgow Coma Score and to the Revised Trauma Score (p<0.0001). CONCLUSION: Pre-Hospital Pediatric Trauma Classification is a simple and reliable method for assessment, triage and recruitment of pediatric trauma resources.OBJETIVO: Avaliar o atendimento pré-hospitalar de crianças e adolescentes em São Paulo, avaliar o banco de dados das Unidades de Suporte Básico (UR) e Avançado (USA) e propor um método simples e eficaz para a avaliação da gravidade do trauma pediátrico na fase pré-hospitalar. MÉTODOS: Uma única central do Corpo de Bombeiros (COBOM) coordena todo o atendimento pré-hospitalar em São Paulo. Dois bancos de dados foram analisados para crianças de 0 a 18 anos de idade, entre 1998 e 2001: um das Unidades de Suporte Básico de Vida (UR- bombeiros) e outra de Unidades de Suporte Avançado (USA - médico e bombeiros). Neste período, o Serviço de Atendimento Médico de Urgência do Estado de São Paulo (SAMU) forneceu relatórios médicos de 604 vítimas, enquanto os bombeiros forneceram relatórios de 12.761 vitimas (UR+USA). A classificação do trauma pré-hospitalar pediátrico é baseada na condição fisiológica, mecanismo de trauma e lesões anatômicas das vítimas. A classificação do trauma pré-hospitalar pediátrico foi comparada à Escala de Coma de Glasgow (GCS) e ao Escore de Trauma Revisado (RTS). RESULTADOS: Houve predominância do sexo masculino em ambos bancos de dados. O mecanismo de trauma mais freqüente foi relacionado a transporte, seguido de quedas. A mortalidade foi 1,6% nas Unidades Básicas e 9,6% no Suporte Avançado. Houve associação entre a classificação do trauma pré-hospitalar pediátrico, Escala de Coma de Glasgow (GCS) e ao Escore de Trauma Revisado (RTS) GCS e RTS (p<0,0001). CONCLUSÃO: A classificação do trauma pré-hospitalar pediátrico é um método simples e confiável para a avaliação, triagem e recrutamento de recursos para o atendimento pré-hospitalar do trauma pediátrico.Universidade Federal de São Paulo (UNIFESP) Department of SurgeryUNIFESP, Department of SurgerySciEL

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Enhancement of sp(3)-bonding in high-bias-voltage grown diamond-like carbon thin films studied by x-ray absorption and photoemission spectroscopy

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    [[abstract]]X-ray absorption near-edge structure (XANES) and valence-band photoemission spectroscopy (VB-PES) were used to elucidate the electronic and mechanical properties of diamond-like carbon (DLC) thin films deposited by the plasma-enhanced chemical vapour deposition method at various bias voltages (Vb) using a C2H2 vapour precursor in an Ar+ atmosphere. The increase of Vb is found to increase and decrease the contents of sp3- and sp2-bonded carbon atoms, respectively, i.e. the films become more diamond-like. The Young's modulus measurements show increases with the increase of the presence of sp3-bonded carbon atoms in the structure of the DLC films.[[notice]]補正完

    Kinetics of biodegradation of diethylketone by Arthrobacter viscosus

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    The performance of an Arthrobacter viscosus culture to remove diethylketone from aqueous solutions was evaluated. The effect of initial concentration of diethylketone on the growth of the bacteria was evaluated for the range of concentration between 0 and 4.8 g/l, aiming to evaluate a possible toxicological effect. The maximum specific growth rate achieved is 0.221 h-1 at 1.6 g/l of initial diethylketone concentration, suggesting that for higher concentrations an inhibitory effect on the growth occurs. The removal percentages obtained were approximately 88%, for all the initial concentrations tested. The kinetic parameters were estimated using four growth kinetic models for biodegradation of organic compounds available in the literature. The experimental data found is well fitted by the Haldane model (R2 = 1) as compared to Monod model (R2 = 0.99), Powell (R2 = 0.82) and Loung model (R2 = 0.95). The biodegradation of diethylketone using concentrated biomass was studied for an initial diethylketone concentration ranging from 0.8–3.9 g/l in a batch with recirculation mode of operation. The biodegradation rate found followed the pseudo-second order kinetics and the resulting kinetic parameters are reported. The removal percentages obtained were approximately 100%, for all the initial concentrations tested, suggesting that the increment on the biomass concentration allows better results in terms of removal of diethylketone. This study showed that these bacteria are very effective for the removal of diethylketone from aqueous solutions.The authors would like to gratefully acknowledge the financial support of this project by the Fundacao para a Ciencia e Tecnologia (FCT), Ministerio da Ciencia e Tecnologia, Portugal and Fundo Social Europeu (FSE). Cristina Quintelas thanks FCT for a Post-Doc grant

    TDP-43 as a potential biomarker for amyotrophic lateral sclerosis:a systematic review and meta-analysis

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    Abstract Background Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are incurable, progressive and fatal neurodegenerative diseases with patients variably affected clinically by motor, behavior, and cognitive deficits. The accumulation of an RNA-binding protein, TDP-43, is the most significant pathological finding in approximately 95% of ALS cases and 50% of FTD cases, and discovery of this common pathological signature, together with an increasing understanding of the shared genetic basis of these disorders, has led to FTD and ALS being considered as part of a single disease continuum. Given the widespread aggregation and accumulation of TDP-43 in FTD-ALS spectrum disorder, TDP-43 may have potential as a biomarker in these diseases. Methods We therefore conducted a systematic review and meta-analysis to evaluate the diagnostic utility of TDP-43 detected in the cerebrospinal fluid (CSF) of patients with FTD-ALS spectrum disorder. Results From seven studies, our results demonstrate that patients with ALS have a statistically significantly higher level of TDP-43 in CSF (effect size 0.64, 95% CI: 0.1–1.19, p = 0.02). Conclusions These data suggest promise for the use of CSF TDP-43 as a biomarker for ALS

    Social conditions of becoming homelessness: qualitative analysis of life stories of homeless peoples

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    Background It is increasingly acknowledged that homelessness is a more complex social and public health phenomenon than the absence of a place to live. This view signifies a paradigm shift, from the definition of homelessness in terms of the absence of permanent accommodation, with its focus on pathways out of homelessness through the acquisition and maintenance of permanent housing, to understanding the social context of homelessness and social interventions to prevent it. However, despite evidence of the association between homelessness and social factors, there is very little research that examines the wider social context within which homelessness occurs from the perspective of homeless people themselves. This study aims to examine the stories of homeless people to gain understanding of the social conditions under which homelessness occurs, in order to propose a theoretical explanation for it. Method Twenty-six semi-structured interviews were conducted with homeless people in three centres for homeless people in Cheshire North West of England. Results The analysis revealed that becoming homeless is a process characterised by a progressive waning of resilience capacity to cope with life challenges created by series of adverse incidents in one’s life. The data show that final stage in the process of becoming homeless is complete collapse of relationships with those close to them. Most prominent pattern of behaviours participants often describe as main causes of breakdown of their relationships are: 1. engaging in maladaptive behavioural lifestyle including taking drugs and/or excessive alcohol drinking 2. Being in trouble with people in authorities. Conclusion Homeless people describe the immediate behavioural causes of homelessness, however, the analysis revealed the social and economic conditions within which homelessness occurred. The participants’ descriptions of the social conditions in which were raised and their references to maladaptive behaviours which led to them becoming homeless, led us to conclude that they believe that their social condition affected their life chances: that these conditions were responsible for their low quality of social connections, poor educational attainment, insecure employment and other reduced life opportunities available to them

    mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression.

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    Schwann cell development is hallmarked by the induction of a lipogenic profile. Here we used amniotic fluid stem (AFS) cells and focused on the mechanisms occurring during early steps of differentiation along the Schwann cell lineage. Therefore, we initiated Schwann cell differentiation in AFS cells and monitored as well as modulated the activity of the mechanistic target of rapamycin (mTOR) pathway, the major regulator of anabolic processes. Our results show that mTOR complex 1 (mTORC1) activity is essential for glial marker expression and expression of Sterol Regulatory Element-Binding Protein (SREBP) target genes. Moreover, SREBP target gene activation by statin treatment promoted lipogenic gene expression, induced mTORC1 activation and stimulated Schwann cell differentiation. To investigate mTORC1 downstream signaling we expressed a mutant S6K1, which subsequently induced the expression of the Schwann cell marker S100b, but did not affect lipogenic gene expression. This suggests that S6K1 dependent and independent pathways downstream of mTORC1 drive AFS cells to early Schwann cell differentiation and lipogenic gene expression. In conclusion our results propose that future strategies for peripheral nervous system regeneration will depend on ways to efficiently induce the mTORC1 pathway
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